Infants born with advanced congenital hydronephrosis due to urethral obstruction in utero have severely damaged kidneys (Type IV cystic disease), hypoplastic lungs and musculoskeletal and abdominal wall deformities. Those that survive neonatal pulmonary insufficiency usually develop renal failure. These devastating developmental consequences of fetal urethral obstruction may be averted if the obstruction is relieved early enough in gestation to allow normal development to proceed. In order to study the pathophysiology of fetal urethral obstruction and theefficacy and feasibility of correction in utero, we have simulated human congenital hydronephrosis by gradually constricting the urethra of fetal lambs and monkeys during the last trimester. An efficient twin gestation fetal lamb model will be used to assess the pathophysionogic consequences of obstruction and its decompression at different stages in gestation, and to study the relationship of oligohydramnios to the development of pulmonary hypoplasia. The fetal rhesus monkey, a more rigorous model, will be used to assess clinical applicability and technical feasibility. In addition to the pathophysiology of obstruction and ts relief we will study the effects of anesthetic and tocolytic agents on uterine contractility and on fetal and maternal well being, develop methods to monitor the fetus and mother during and after fetal surgery, refine techniques for fetal exposure and manipulation, and develop techniques for percutaneous sonographically guided placement of Silastic shunts. By studying the pathophysiology of experimental fetal urinary tract obstruction and its relief, we hope to determine if in utero correction should be attempted, when in gestation it will be effective, and how it can be safely accomplished. Congenital hydroephrosis may be the first birth defect amenable to correction before birth.